Solid preparation, method for producing solid reparation, and method for generating hydrogen

ABSTRACT

One solid preparation of the present invention mainly includes silicon fine particles, and has a capability of generating hydrogen. In addition, one specific example of the solid preparation mainly includes silicon fine particles having a crystallite diameter principally of 1 nm or more and 100 nm or less, and exhibits a capability of generating hydrogen in an amount of 3 ml/g or more when brought into contact with a water-containing liquid having a pH value of 7 or more. In this solid preparation, hydrogen is generated when the silicon fine particles are brought into contact with a water-containing liquid having a pH value of 7 or more. Therefore, taking advantage of the characteristics of the solid preparation, generation of hydrogen is promoted in, for example, a gastrointestinal tract where the pH value is 7 or more due to secretion of pancreatic fluid after passage through the stomach after oral ingestion.

RELATED APPLICATIONS

This application is a U.S. National Stage filing under 35 U.S.C. § 371of PCT Application No. PCT/JP2017/000749, filed Jan. 12, 2017, whichclaims priority to Japanese Application No. 2016-015123 filed Jan. 29,2016, which applications are incorporated herein by reference, in theirentirety, for any purpose.

TECHNICAL FIELD

The present invention relates to a solid preparation for generatinghydrogen, a method for producing the solid preparation, and a method forgenerating hydrogen.

BACKGROUND ART

Active oxygen derived from oxygen generated in the body and oxygen takenin from the lung is present in a body of an animal such as a human.Active oxygen is known to oxidize and damage cells that form a livingbody while it is necessary for life support. For example, active oxygen,particularly a hydroxyl radical which has the strongest oxidizing powerin active oxygen is considered to cause various diseases such as cancer,stroke, myocardial infarction, diabetes, other lifestyle diseases, andskin disorders such as skin aging and dermatitis. Therefore, it isdesirable that excess active oxygen, particularly a hydroxyl radical,which has not been used in a reaction useful for a living body, beprevented from being present in the body wherever possible.

Hydroxyl radicals produced in the body are eliminated by reacting withsome substances. Hydrogen is known as an example of substances thateliminate hydroxyl radicals. It is water that is produced by hydrogenreacting with hydroxyl radicals, and water does not produce substancesharmful to a living body. Thus, a device for producing hydrogen watercontaining hydrogen which eliminates hydroxyl radicals in the body hasbeen proposed (e.g. Patent Document 1).

However, hydrogen in hydrogen water is easily diffused into air. Thus,for taking hydrogen in the body in an amount necessary for eliminatinghydroxyl radicals, it is necessary that the concentration of dissolvedhydrogen in hydrogen water be kept high. Therefore, with a method inwhich hydrogen water is ingested, it is not easy to take hydrogen in thebody in an amount sufficient to react the hydrogen with hydroxylradicals in the body. Thus, for making to easily take hydrogen in thebody, a hydrogen-containing composition containing hydrogen and asurfactant has been proposed (Patent Document 2).

PRIOR ART DOCUMENTS Patent Documents

Patent Document 1: Japanese Patent Publication No. 5514140

Patent Document 2: Japanese Patent Laid-open Publication No. 2015-113331

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

However, even when high-concentration hydrogen water is ingested, theamount of hydrogen contained in 1 liter of hydrogen water is only 18 mlin terms of a gas, and in addition, much of hydrogen in hydrogen wateris gasified in the stomach and intestines. Thus, there is the problem ofcausing pneumophagia (so-called “burp”) because a sufficient amount ofhydrogen is not necessarily taken in the body. On the other hand, when ahydrogen-containing composition with hydrogen encapsulated by asurfactant is ingested, it is necessary to ingest a large amount of thehydrogen-containing composition for taking a sufficient amount ofhydrogen in the body. In addition, there may arise the above-mentionedproblem that hydrogen is released in the stomach.

The present invention greatly contributes to solving at least one of theabove-described technical problems, so that a sufficient amount ofhydrogen is easily taken in the body for eliminating hydroxyl radicalsin the body. In addition, the present invention can contributeparticularly to solving the above-described problem that a hydrogen gasgoes out of the body from the inside of the stomach, and easily andefficiently taking hydrogen in the body.

Solutions to the Problems

The present inventors have extensively conducted analysis and studies onsilicon fine particles having certain characteristics. Resultantly, thepresent inventors have found that very interestingly, the silicon fineparticles hardly generate hydrogen even when brought into contact with awater-containing liquid (e.g. water or an aqueous solution) having a pHvalue in a numerical range, but the silicon fine particles may markedlygenerate hydrogen when brought into contact with a water-containingliquid having a pH value in another numerical range. In addition, it hasbeen found that the generation amount of the hydrogen considerablyincreases as the pH value increases. In addition, the present inventorshave found that by applying the above-mentioned facts, hydrogen can begenerated in gastrointestinal tracts after passage through the stomachand after secretion of pancreatic fluid (typically the small intestineand/or the large intestine) while hydrogen is prevented from beinggenerated in the stomach.

A hydrogen generation mechanism using a reaction of silicon fineparticles with water molecules is shown in the following formula (1).However, the present inventors have found that the reaction shown in theformula (1) hardly proceeds when silicon fine particles are brought intocontact with a water-containing liquid having a low pH value (typicallya pH value of less than 7), and the reaction proceeds when silicon fineparticles are brought into contact with a water-containing liquid havinga pH value of 7 or more (a basic water-containing liquid (hereinafter,referred to as an alkaline water-containing liquid) having a pH value ofpreferably more than 7, more preferably more than 7.4). The presentinvention has been made on the basis of the above-mentioned points ofviewpoint.Si+2H₂O→SiO₂+2H₂  (Chemical Formula 1)

One solid preparation of the present invention is a solid preparationwhich mainly includes silicon fine particles, and has a capability ofgenerating hydrogen. A more specific example of a solid preparationmainly includes silicon fine particles having a crystallite diameterprincipally of 1 nm or more and 100 nm or less, and exhibits acapability of generating hydrogen in an amount of 3 ml/g or more whenbrought into contact with a water-containing liquid having a pH value of7 or more.

In this solid preparation, hydrogen is generated when silicon fineparticles are brought into contact with the water-containing liquid. Inparticular, when silicon fine particles are brought into contact with awater-containing liquid having a pH value of 7 or more, a large amountof hydrogen is generated. Therefore, taking advantage of thecharacteristics of the solid preparation, generation of hydrogen ispromoted in, for example, a gastrointestinal tract where the pH value is7 or more due to secretion of pancreatic fluid after passage through thestomach after oral ingestion. In addition, when the pH value is morethan 7 (alkali range in a narrower sense), generation of hydrogen isfurther promoted. As a result, a large amount of hydrogen can beselectively generated, so to speak, in a specific pH value range. In thepresent application, the expression of “crystallite” is employed ratherthan the expression of “crystal grain (or crystal particle)” when thediameter of the crystal is in the “nm order”. On the other hand, theexpression of “crystal grain (or crystal particle)” is employed when thediameter of the crystal is in the “μm order”.

One method for generating hydrogen according to the present inventionincludes: a first contact step of bringing a solid preparation, whichmainly includes silicon fine particles having a crystallite diameterprincipally of 1 nm or more and 100 nm or less and which exhibits acapability of generating hydrogen in an amount of 3′ ml/g when broughtinto contact with a water-containing liquid having a pH value of 7 ormore, into contact with a first water-containing liquid having a pH ofless than 7; and a second contact step of bringing the fine siliconparticles into contact with a second water-containing liquid having a pHvalue of 7 or more after the first contact step.

The method for generating hydrogen includes the steps of bringing thesilicon fine particles into contact with the first water-containingliquid having-a pH value of less than 7 that is a pH value at whichhydrogen is not generated or hardly generated; and bringing the siliconfine particles into contact with the second water-containing liquidhaving a pH value of 7 or more that is a pH value at which generation ofhydrogen is promoted. Thus, it is possible to perform so-calledselective generation of hydrogen at a pH value in a specific range.Taking advantage of the characteristics of the method, generation ofhydrogen is promoted by bringing the solid preparation into contact withthe second water-containing liquid in, for example, a gastrointestinaltract where the pH value is 7 or more due to secretion of pancreaticfluid after passage through the stomach after oral ingestion. Inaddition, when the pH value of the second water-containing liquid ismore than 7 (alkali range in the narrower sense), generation of hydrogenis further promoted.

The method for generating hydrogen can be considered as a method forusing the solid preparation when seen from a different angle.

In addition, one method for producing a solid preparation according tothe present invention includes the step of finely dividing siliconparticles, which have a crystal grain diameter of more than 1 μm, by abead mill method to obtain silicon fine particles having a crystallitediameter principally of 1 nm or more and 100 nm or less. In addition,the production method is a method for producing a solid preparationwhich exhibits a capability of generating hydrogen in an amount of 3ml/g or more when the silicon fine particles are brought into contactwith a water-containing liquid having-a pH value of 7 or more.

Here, the “silicon fine particles” in the present application include,as main particles, silicon nanoparticles having an average crystallitediameter at a nano level, specifically a crystalline diameter of 1 nm ormore and 100 nm or less. In a narrower sense, the “silicon fineparticles” in the present application include, as main particles,silicon nanoparticles having an average crystallite diameter at a nanolevel, specifically a crystalline diameter of 1 nm or more and 50 nm orless. In addition, in the present application, the silicon fineparticles include not only those in which silicon nanoparticles aredispersed, but also those in which a plurality of silicon nanoparticlesare naturally gathered to form aggregates having a size close to a μmsize (generally 0.1 μm or more and 1 μm or less).

In addition, the “water-containing liquid” in the present application iswater or an aqueous solution, and encompasses gastrointestinal tractinternal fluid of animals (including humans). The “gastrointestinaltract internal fluid” encompasses gastric fluid, pancreatic fluid, andsmall intestine internal fluid and large intestine internal fluid aftersecretion of pancreatic fluid. In addition, the material of the “pHadjusting agent” in the present application is not particularly limitedas long as it is an agent capable of adjusting the pH value to fallwithin an alkali range of mote than 7.4 (hereinafter, referred to as an“alkali agent”). For example, when the solid preparation is used as anindustrial agent, the alkali agent may encompass potassium carbonate,sodium carbonate, sodium hydrogencarbonate, potassium carbonate, sodiumhydroxide, potassium hydroxide, and the like. In addition, when thesolid preparation is used as an active oxygen neutralizing agent in aliving body, an alkali agent recognized as a food additive can be used.The most preferred alkali agent is sodium hydrogencarbonate. Sodiumhydrogencarbonate is widely used as a food additive because sodiumhydrogencarbonate has a plurality of advantages such that it has a pHvalue adjustment function required in the present invention, and isexcellent in safety and versatility.

In addition, the aspect of the “silicon fine particles” in the presentapplication includes an orally ingestible solid preparation as a statebefore use. Here, the silicon fine particles can be aggregated in anatural state to form aggregates having a diameter size of μm order(e.g. 1 μm). In the present application, silicon fine particles may beartificially put together by addition of a binding agent, compression orthe like to form a lump solid preparation having such a size that it canbe picked up by human fingers. The lump solid preparation is sometimesreferred to as a “lump preparation” for discriminating the lump solidpreparation from the above-mentioned “aggregate”. Typical examples ofthe “lump preparation” include tablets and capsule preparations. The“solid preparation” of the present application encompasses such lumppreparations, and further encompasses granular and powdered preparationswhich assume a powdery form rather than a lump form.

Effects of the Invention

With one solid preparation of the present invention, a large amount ofhydrogen is generated from silicon fine particles when the silicon fineparticles are brought into contact with a water-containing liquid havinga pH value of 7 or more. As a result, a large amount of hydrogen can begenerated, so to speak, selectively in a specific pH value range wherethe pH value is 7 or more.

In addition, one method for generating hydrogen according to the presentinvention includes the steps of: bringing the silicon fine particlesinto contact with the first water-containing liquid having a pH value ofless than 7 that is a pH value at which hydrogen is not generated orhardly generated; and bringing the silicon fine particles into contactwith the second water-containing liquid having a pH value of 7 or morethat is a pH value at which generation of hydrogen is promoted. Thus,hydrogen can be generated, so to speak, selectively at a pH value in-aspecific range.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows photographs ((a): perspective view and (b): side view) of asolid preparation according to a first embodiment of the presentinvention.

FIG. 2 is a graph showing the amounts of hydrogen generated in Examples1 to 3 and Reference Example 1.

FIG. 3 shows a photograph of a state in which the solid preparationaccording to the first embodiment of the present invention is immersedin pure water for 60 seconds to disintegrate the dosage form.

FIG. 4 is a graph showing hydrogen generation amounts in Examples 4 to8.

FIG. 5 is a graph showing hydrogen generation amounts in Examples 9 and10.

FIG. 6 is a graph showing a hydrogen generation amount in Example 11.

FIG. 7 is a graph showing hydrogen generation amounts in Examples 12 and13 and Reference Example 2.

EMBODIMENTS OF THE INVENTION

Embodiments of the present invention will be described in detail withreference to the accompanying drawings.

[1] Solid Preparation and Method for Producing the Solid Preparation

First Embodiment

A solid preparation of this embodiment is, a solid preparation whichmainly includes silicon fine particles, and has a capability ofgenerating hydrogen. For the solid preparation of this embodiment,silicon fine particles (hereinafter, sometimes referred to as “siliconnanoparticles” for the sake of convenience) are used which are obtainedby finely dividing a commercially available high-purity silicon particlepowder (manufactured by Kojundo Chemical Lab. Co., Ltd., particlediameter distribution: <φ 5 μm (typically, silicon particles having acrystal grain diameter of more than 1 μm, purity: 99.9, i-type silicon)as silicon particles by a bead mill method and which include siliconnanoparticles as main particles.

Specifically, 15 g of a high-purity Si powder is dispersed in 300 ml ofisopropyl alcohol (IPA) of 99% or more, φ 0.5 μm zirconia beads (volume:300 ml) are added, and the mixture is finely divided by performinggrinding (one-step grinding) at a rotation speed of 2500 rpm for 4 hoursusing a bead mill apparatus (RMB Badge-Type Ready Mill manufactured byAIMEX CO., Ltd.).

Using a stainless steel material filter (mesh: 0.35 mm) attached to abead separation container (manufactured by AIMEX CO., Ltd.), siliconnanoparticles including beads are subjected to suction filtration toseparate the beads from the silicon nanoparticles. The IPA solutioncontaining silicon nanoparticles separated from the beads is heated to40° C. using a vacuum evaporator, so that IPA is evaporated to obtainsilicon nanoparticles.

The silicon nanoparticles obtained by the above-mentioned method mainlyinclude silicon fine particles having a crystallite diameter principallyof 1 am or more and 100 nm or less. More specifically, as a result ofmeasuring the silicon nanoparticles by an X-ray diffractometer (SMARTLABmanufactured by Rigaku Corporation), the following values were obtainedas an example. In a volume distribution, the mode diameter was 6.6 nm,the median diameter was 14.0 nm, and the average crystallite diameterwas 20.3 nm.

The silicon nanoparticles were observed using a scanning electronmicroscope (SEM), and the result showed that the silicon nanoparticleswere partially aggregated to form a slightly large formless aggregatesof about 0.5 am or less. In addition, individual silicon nanoparticleswere observed using a transmission electron microscope (TEM), many ofthem had a crystallite diameter of about 2 nm or more and 20 nm or less.

5 mg of the silicon nanoparticles are mixed with 495 mg of a sodiumhydrogencarbonate powder (manufactured by Wako Pure Chemical Industries,Ltd., purity: 99.5%). The mixture is kneaded, and formed into a columnarlump body having a diameter of 8 mm and a height of 4 mm by a tabletingmethod, so that a tablet shown in FIG. 1 can be obtained. FIG. 1(a) is aperspective view of a tablet as one example, and FIG. 1(b) is a sideview of the tablet as one example. The tablet is one example of a lumppreparation as a solid preparation.

Second Embodiment

50 mg of citric acid (manufactured by Wako Pure Chemical Industries,Ltd., purity: 99.5%) is further added to 5 mg of the siliconnanoparticles used in the first embodiment and 495 mg of a sodiumhydrogencarbonate powder, and the mixture is kneaded to form a columnarlump body having a diameter of 8 mm and a height of 6 mm, so that thesame tablet as the tablet shown in FIG. 1 can be obtained.

Third Embodiment

Except that the amount of citric acid is 200 mg, the same treatment asin the second embodiment is performed to obtain a tablet. This tablet isa columnar tablet similar to the tablet shown in FIG. 1, and has adiameter of 8 mm and a height of 10 mm.

Fourth Embodiment

The silicon nanoparticles described in the first embodiment are immersedin a hydrofluoric acid aqueous solution at a concentration of 5% by massfor 10 minutes. Thereafter, using a fluororesin membrane filter of 100nm mesh, a filtration treatment in air is performed to trap the siliconnanoparticles on the membrane filter. The membrane filter is held on afluororesin beaker while the silicon nanoparticles are trapped on thefilter. The hydrofluoric acid component is removed by adding ethanoldropwise to the filter held on the beaker. The silicon nanoparticles onthe membrane filter from which the hydrofluoric acid component has beenremoved are dried in air for about 30 minutes. By the above-describedprocedure, silicon nanoparticles treated with hydrofluoric acid areobtained.

Here, by X-ray photoelectron spectrometry (XPS method), the presentinventors measured the thickness of a silicon oxide film on the surfacesof the silicon nanoparticles treated with hydrofluoric acid by theabove-described method. Silicon nanoparticles which had not been treatedwith hydrofluoric acid had a silicon dioxide film having a thickness ofabout 1.6 nm. On the other hand, when the hydrofluoric acid treatmentwas performed, the oxide film was removed with high reliability to theextent that the oxide film had a thickness of 0.1 nm or less. Therefore,the silicon nanoparticles treated with hydrofluoric acid had littleoxide film.

In the fourth embodiment, silicon nanoparticles from which an oxide filmhas been removed by the above-described treatment are used in place ofthe silicon nanoparticles in the first embodiment. A tablet was obtainedby carrying out the same procedure as iii the second embodiment forother conditions. This tablet is a columnar tablet similar to the tabletshown in FIG. 1, and has a diameter of 8 mm and a height of 4 mm.

Fifth Embodiment

200 mg of the citric acid described in the second embodiment is furtheradded to and mixed with the silicon nanoparticles treated withhydrofluoric acid in the fourth embodiment. Thereafter, the sametreatment as in the second embodiment is performed to obtain a tablet.This tablet is a columnar tablet similar to the tablet shown in FIG. 1,and has a diameter of 8 mm and a height of 10 mm.

Sixth Embodiment

The same high-purity silicon particle powder as that used in the firstembodiment (typically, silicon particles having a crystal grain diameterof more than 1 μm) is ground in one step in accordance with theprocedure described in the first embodiment. Subsequently, using astainless steel material filter (mesh: 0.35 mm) attached to a beadseparation container (manufactured by AIMEX CO., Ltd.), zirconia beadsof ϕ 0.5 μm (volume: 300 ml) to be used for one-step grinding aresubjected to suction filtration to separate the beads from the siliconnanoparticles. Zirconia beads of 0.3 μm (volume: 300 ml) are added tothe silicon nanoparticle containing solution from which beads have beenseparated, and the mixture is finely divided by performing grinding(two-step grinding) at a rotation speed of 2500 rpm for 4 hours.

In silicon nanoparticles including beads, the beads are separated fromthe silicon nanoparticles using a bead separator with a stainless steelmaterial filter (mesh: 0.35 mm) attached thereto. The IPA solutioncontaining silicon nanoparticles separated from the beads is heated to40° C. using a vacuum evaporator in the same manner as in the firstembodiment, so that IPA is evaporated to obtain silicon nanoparticles.

[2] Method for Generating Hydrogen

Seventh Embodiment

Animals are caused to orally ingest the tablets described in the firstto fifth embodiments. First, as a first contact step, for example, thetablet is brought into contact with gastric fluid as a firstwater-containing liquid having a pH value of less than 7 (morespecifically, a pH value of about 3 to 4) in the stomach. In addition,for example, the tablet passes through the stomach, and as a secondcontact step, the tablet is brought into contact with gastrointestinaltract fluid as a second water-containing liquid having a pH value of 7or more in a gastrointestinal tract after the stomach, specifically thesmall intestine and/or the large intestine.

Thus, for example, by causing an animal (such as a human) to orallyingest the solid preparation, the silicon nanoparticles (tablet as onemore specific example) in each of the embodiments are brought intocontact with the first water-containing liquid having a pH value of lessthan 7 in the first contact step, and brought into contact with thesecond water-containing liquid having a pH value of 7 or more in thesubsequent second contact step, so that hydrogen can be generated in thesecond contact step. Therefore, the solid preparation containing thesilicon nanoparticles of each of the embodiments can exhibit aremarkable capability of generating hydrogen when brought into contactwith a water-containing liquid having a pH value of 7 or more.

The tablet in this embodiment is brought into contact with the firstwater-containing liquid (gastric fluid) in the stomach as the firstcontact step, and then brought into contact with the secondwater-containing liquid in a gastrointestinal tract after the stomach(more specifically the small intestine and/or the large intestine). Inthe gastrointestinal tract after passage through the stomach, secretionof pancreatic fluid causes the second water-containing liquid to has apH value of 7 or more (in an alkali range in a narrower sense). Thus, itis worth noting that in this embodiment, hydrogen can be generated, soto speak, selectively under such conditions that generation of hydrogenis desired.

Utilization of the above-described action and effect ensures thathydrogen in an amount sufficient to eliminate hydroxy radicals in thebody of, for example, an animal (such as a human) can be generated inthe intestine with a high absorption rate, and thus easily taken in thebody. Particularly in the case of humans, the solid preparation does notgenerate much hydrogen in the stomach where the pH value is much lowerthan 7. On the other hand, the solid preparation is disintegrated into apowdery form by passing through the stomach, and reaches the smallintestine and/or the large intestine. In the small intestine and/or thelarge intestine, pancreatic fluid is secreted, and therefore the pHvalue is in an alkali range of about 7.5 to 8.9, so that the solidpreparation generates much hydrogen. This indicates that hydrogenhaving, an antioxidative effect can be more reliably absorbed in thehuman body (temperature is generally 35° C. or higher and 37° C. orlower).

The example of application of the solid preparation using the siliconnanoparticles described in each of the first to fifth embodiments is notlimited to a tablet. For example, even when a capsule preparation withpowdery silicon nanoparticles (including those formed into aggregates)encapsulated in a capsule is employed in place of a tablet, the sameeffect as the above-mentioned effect can be exhibited. As will bedescribed later, silicon nanoparticles can generate much hydrogen whenthe nanoparticles are in the powdery form having a large surface arearather than being in a lump form, but the nanoparticles are orallyingested easily when formed into a tablet or a capsule preparation. Inaddition, when the nanoparticles are formed into a tablet or a capsulepreparation, they maintain a lump form to some extent, but areincreasingly disintegrated to assume a powdery form after passingthrough the stomach. Thus, in the stomach where it is desired tosuppress the hydrogen generation reaction, the surface area of thesilicon nanoparticles exposed to gastric fluid and/or gastric contentscan be reduced, and in the small intestine and/or large intestine whereit is desired to promote the hydrogen generation reaction, the surfacearea of the silicon nanoparticles exposed to the water-containing liquidcan be increased.

In addition, the solid preparation may be a granular preparation. Thegranular preparation assumes a powdery form in an earlier stage afterbeing orally ingested as compared to tablets and capsules. However,since the pH value of gastric fluid is low (less than 7), thepreparation generates little hydrogen even when assuming a powdery formimmediately after reaching the stomach, and generates hydrogen in thepresence of water after passage through the stomach.

The solid preparation may be a powdered preparation. The powderedpreparation is easy to handle when the solid preparation is used as, forexample, a constituent component of a food such as a health food, e.g. afood additive. When the solid preparation is used as a food additive,silicon fine particles having a crystallite diameter of 1 nm or more and100 nm or less may be mixed and used as the solid preparation accordingto the present invention. Preferably, the silicon fine particles arecontained in an amount of 1% by mass or more. The upper limit of thecontent of silicon fine particles is not specified, but is preferably40% by mass or less with consideration given to the taste.

In addition, an example of a covering layer applicable to a tablet is aknown enteric material hardly soluble in the stomach, which is a coatingagent that covers the outermost layer of the tablet. In addition, anexample of a covering layer applicable to a capsule preparation is acapsule itself which encapsulates silicon fine particles (mainlyaggregates of silicon fine particles), and is produced from a-knownenteric material hardly soluble in the stomach.

As described above, an example of a solid preparation suitable as anapplication of the silicon nanoparticles according in this embodiment isa tablet which is a lump preparation which is easily orally ingested ina sufficient amount, or a capsule preparation in which powdery siliconfine particles (including those formed into aggregates) are encapsulatedin a capsule. When a tablet is employed, a disintegrating agent may befurther included. For the disintegrating agent, a known material can beemployed. In addition, a preferred example of a more suitabledisintegrating agent is an organic acid, and the most preferred exampleis citric acid. Here, the organic acid can also function as a bindingagent that brings silicon nanoparticles into a lump form.

In addition, the temperature condition of the second water-containingliquid for generation of hydrogen in each of the embodiments is notlimited. However, when the temperature of the second water-containingliquid is 35° C. or higher, the hydrogen generation reaction ispromoted. The second water-containing liquid is not limited to a liquidin the human body. When the temperature of the second water-containingliquid is 35° C. or higher and 60° C. or lower, generation of hydrogenis promoted with high reliability. However, the upper limit of thetemperature of the second water-containing liquid is not limited. Forexample, when the solid preparation in this embodiment is used as anindustrial chemical, the temperature may be higher than 50° C. However,when the temperature becomes higher, there is the problem that equipment(including a container) is required to have high heat resistance, andcare is needed for handling. Therefore, the temperature is preferably100° C. or lower even when the solid preparation is used as anindustrial chemical.

EXAMPLES

Hereinafter, the embodiments will be described more in detail by way ofexamples, but the embodiments are not limited to these examples.

Example 1

First, in Examples 1 to 3 below, silicon nanoparticles themselves areevaluated as preliminary examples without carrying out a tabletingprocess in a tableting method. Specifically, as Example 1, siliconnanoparticles ground in one step were used to conduct an experimentbefore the silicon nanoparticles were processed into a solidpreparation.

10 mg of the silicon nanoparticles described in the first embodimentwere added as a powdered preparation (i.e. the silicon nanoparticleswere not either mixed with a sodium hydrogencarbonate or kneaded) in aglass bottle having a volume of 100 ml (borosilicate glass having athickness of about 1 mm, Laborane Screw Tubular Bottle manufactured byAS ONE Corporation.). 30 ml of tap water having a pH value of 7.1 wasadded in the glass bottle, the glass bottle was hermetically sealedunder the temperature condition of a liquid temperature of 25° C., theconcentration of hydrogen in the liquid in the glass bottle wasmeasured, and the hydrogen generation amount was determined using themeasured hydrogen concentration. For measurement of the hydrogenconcentration, a portable dissolved hydrogen meter (Model: DH-35Amanufactured by DKK-TOA CORPORATION) was used.

Example 2

In Example 2, the same procedure as in Example 1 was carried out exceptthat potassium hydroxide was dissolved in ultrapure water to set the pHvalue to 8.0.

Example 3

In Example 3, the same procedure as in Example 1 was carried out exceptthat potassium hydroxide was dissolved in ultrapure water to set the pHvalue to 8.6.

Reference Example 1

In Reference Example 1, the same procedure as in Example 1 was carriedout except that ultrapure water was used in place of tap water, and thepH value of the liquid in the glass bottle was set to 7.0. In addition,in Comparative Example 1 being an example in which a water-containingliquid had a pH value of less than 7, evaluation was performed under thesame conditions as in Example 1 except that hydrochloric acid was addedas a pH value adjusting agent to ultrapure water to set the pH value to1.5.

FIG. 2 shows results for hydrogen generation in Examples 1 to 3 that arepreliminary examples, and Reference Example 1. The abscissa of the graphrepresents a time (minutes) during which silicon nanoparticles areimmersed in water-containing liquids to be kept in contact withwater-containing liquids having various pH values, and the ordinate ofthe graph represents a hydrogen generation amount. As shown in FIG. 2,it has been found that a large amount of hydrogen can be generated underthe condition of a pH value of more than 7. In addition, such aninteresting result has been obtained that the hydrogen generation amountper certain time increases as the pH value increases, i.e. thealkalinity becomes stronger. Specifically, in Examples 2 and 3 with a pHvalue of 8 or more, the hydrogen generation amount was remarkably largerthan that in Example 1 with a pH value of less than 8. This indicatesthat it is preferable to bring the silicon nanoparticles into contactwith a water-containing liquid having a pH value of 8 or more because alarge amount of hydrogen can be generated in a short time. InComparative Example 1 (not shown), hydrogen was generated in only a verysmall amount of 2 ml/g over 5 hours.

Based on the results of the foregoing preliminary examples (Examples 1to 3), the present inventors performed evaluation shown in each ofExample 4 and subsequent examples for the solid preparation processedusing the a tableting method.

Example 4

First, as Example 4, one tablet produced through the treatment describedin the first embodiment was added in a glass bottle having a volume of30 ml. 30 ml of pure water (pH value: 7.0) as an example of awater-containing liquid was added in the glass bottle to immerse thetablet in the pure water, and the liquid temperature was kept at 25° C.Under this condition, the glass bottle was hermetically sealed, thehydrogen concentration of hydrogen water generated in the glass bottlewas measured using the apparatus described in Example 1, and thehydrogen generation amount was determined.

The tablet gradually lost its shape in the pure water with elapse oftime. Specifically, about 60 seconds after the tablet was brought intocontact with the pure water, sodium hydrogencarbonate was dissolved inthe liquid, and the silicon nanoparticles were partially settled andleft on the bottom of the container while being almost uniformlydiffused in the liquid as shown in FIG. 3. As a result, the tabletsubstantially lost its original shape, and assumed a powdery form (orfine powdery form; hereinafter, referred to collectively as a “powderyform”) (hereinafter, a phenomenon in which a solid dosage form isdisintegrated into a powdery form is referred to as “disintegration”.Dissolution of a capsule of a capsule preparation encapsulating a powderalso means that a dosage form is disintegrated, and exposure of a powderby dissolution of a capsule is also encompassed in “disintegration”). Inthis example, sodium hydrogencarbonate released with disintegration ofthe tablet was dissolved in water, and therefore the pH value of thewater-containing liquid in the glass bottle increased to 8.3.

Example 5

Example 5 is an example in which a tablet produced through the treatmentdescribed in the second embodiment was used. The tablet was almostwholly disintegrated into a powdery form about 5 minutes after beingbrought into contact with pure water under the temperature condition ofa liquid temperature of 25° C. In the process of disintegration of thetablet (i.e. until 90 minutes after the tablet is brought into contactwith pure water), sodium hydrogencarbonate and citric acid are releasedwith disintegration of the tablet, so that the water-containing liquidhas a pH value of 8.6.

Example 6

In Example 6, the tablet prepared in accordance with the proceduredescribed in the third embodiment was used as a tablet. The tablet wasalmost wholly disintegrated into a powdery form about 5 minutes afterbeing brought into contact with pure water under the temperaturecondition of a liquid temperature of 25° C. In the process ofdisintegration of the tablet (i.e. until 90 minutes after the tablet isbrought into contact with pure water), sodium hydrogencarbonate andcitric acid are released with disintegration of the tablet, so that thewater-containing liquid has a pH value of 8.2.

Example 7

In Example 7, the tablet prepared in accordance with the proceduredescribed in the second embodiment was used as a tablet. In addition,the glass bottle was held in a thermostatic bath to keep, the watertemperature at 37° C. As the water-containing liquid, pure water havinga pH value of 7.0 was used. The tablet was almost wholly disintegratedinto a powdery form about 5 minutes after being brought into contactwith pure water. Sodium hydrogencarbonate and citric acid are releasedwith disintegration of the tablet, so that the water-containing liquidhas a pH value of 8.6.

Example 8

In Example 8, the tablet prepared in accordance with the proceduredescribed in the third embodiment was used as a tablet. In addition, theglass bottle was held in a thermostatic bath to keep the watertemperature at 37° C. As the water-containing liquid, pure waterhaving-a pH value of 7.0 was used. The tablet was almost whollydisintegrated into a powdery form about 5 minutes after being broughtinto contact with pure water. Sodium hydrogencarbonate and citric acidare released with disintegration of the tablet, so that thewater-containing liquid has a pH value of 8.3.

FIG. 4 shows results in Examples 4 to 8. In FIG. 4, the abscissarepresents a time (minutes) during which the tablet is kept in contactwith the water-containing liquid, and the ordinate of the graphrepresents a hydrogen generation amount.

In Example 4, the dosage form of the tablet was disintegrated as shownin FIG. 3, so that sodium hydrogencarbonate was released. In addition,as shown in FIG. 4, the hydrogen generation amount increased with elapseof the contact time between the tablet and the water-containing liquid.

In addition, comparison of Example 5 with Example 7 and comparison ofExample 6 with Example 8 showed that the hydrogen generation amountincreased under the temperature condition of 37° C. close to the bodytemperature. Specifically, it is worth noting that in Examples 9 and 10,it was confirmed that hydrogen was generated in an amount of 20 ml/g ormore in 150 minutes (two and a half hours).

Further, comparison between results in Examples 1 to 3 in which siliconnanoparticles were brought into contact with the water-containing liquidwhile being in a powdery form and results in Examples 4 to 6 in whichsilicon nanoparticles were used as the solid preparation shows that alarger amount of hydrogen can be generated when the siliconnanoparticles are brought into contact with the water-containing liquidwhile being in a powdery form. However, powdery silicon fine particlesare difficult to orally ingest and deliver into the gastrointestinaltract. Thus, in this example, the silicon fine particles are formed intoa solid preparation such as a tablet or a capsule preparation. As shownin FIG. 3, the solid preparation is disintegrated into a powdery formwhen kept in contact with the water-containing liquid for a certaintime. Thus, the solid preparation in this example is suitably used suchthat the solid preparation is kept in contact with a water-containingliquid which does not actively generate hydrogen and which has a pHvalue of less than 7, so that disintegration of the solid preparation ispromoted, and the solid preparation in a powdery form to some extent isbrought into contact with a water-containing liquid having a pH value of7 or more, preferably more than 7.4, more preferably 8 or more, so thatgeneration of hydrogen is promoted.

Example 9

In Example 9, the tablet prepared in accordance with the proceduredescribed in the fourth embodiment was used as a tablet. As thewater-containing liquid, pure water having a pH value of 7.0 was used.The tablet was almost wholly disintegrated into a powdery form about 5minutes after being brought into contact with pure water, and thewater-containing liquid had a pH value of 8.6.

Example 10

In Example 10, the tablet prepared in accordance with the proceduredescribed in the fifth embodiment was used as a tablet. As thewater-containing liquid, pure water having a pH value of 7.0 was used.The tablet was almost wholly disintegrated into a powdery form about 5minutes after being brought into contact with pure water, and thewater-containing liquid had a pH value of 8.2.

FIG. 5 shows results in Examples 9 and 10. In addition, for facilitatingcomparison, the results in Examples 4 to 6 are also shown. In addition,the abscissa of the graph represents a time (minutes) during which thetablet is kept in contact with the water-containing liquid, and theordinate of the graph represents a concentration of hydrogen in theglass bottle. Specifically, it is worth noting that in Examples 9 and10, it was confirmed that hydrogen was generated in an amount of 20 ml/gor more in 150 minutes (two and a half hours).

Example 11

As Example 11, generation of hydrogen by reaction of siliconnanoparticles with water was observed using surface-treated siliconnanoparticles in place of the silicon nanoparticles in Example 1.Specifically, 2.5 mg of the silicon nanoparticles described in thefourth embodiment were added in the same glass bottle as that used inExample 1. 110 ml of water having a sodium hydrogencarbonateconcentration of 0:03% by mass and a pH value of 8.4 was added in theglass bottle to eliminate void portions, the glass bottle washermetically-sealed under the temperature condition of a liquidtemperature of 37° C., the concentration of hydrogen in the liquid inthe glass bottle was measured, and the hydrogen generation amount wasdetermined using the measured hydrogen concentration. Measurement of thehydrogen concentration was performed in the same manner as in Example 1.

In this example, 397 ml (milliliters) of hydrogen per 1 g of siliconnanoparticles was generated by the reaction for 12 hours as shown inFIG. 6. This hydrogen generation amount corresponds to the amount ofhydrogen contained in 22 l (liters) of saturated hydrogen water having ahydrogen concentration of 1.6 ppm. It is worth noting that such anextremely large amount of hydrogen is generated even after a long,period of time (e.g. after 12 hours).

Example 12

In Example 12, silicon nanoparticles obtained by grinding siliconparticles in two steps were used as a solid preparation. Specifically,silicon nanoparticles ground in two steps in accordance with theprocedure described in the sixth embodiment were obtained.

The obtained silicon nanoparticles were measured by an X-raydiffractometer (SMARTLAB manufactured by Rigaku Corporation).Resultantly, in a volume distribution, the mode diameter was 5.8 nm, themedian diameter was 9.6 nm, and the average crystallite diameter was12.2 nm.

2.5 mg of silicon nanoparticles ground in two steps in accordance withthe above-described procedure was added in a 100 ml-volume glass bottlesimilar to that in Example 11. 110 ml of water having a sodiumhydrogencarbonate concentration of 0.03% by mass and a pH value of 8.4was added in the glass bottle, the glass bottle was hermetically sealedunder the temperature condition of a liquid temperature of 37° C., theconcentration of hydrogen in the liquid in the glass bottle wasmeasured, and the hydrogen generation amount was determined using themeasured hydrogen concentration. Measurement of the hydrogenconcentration was performed in the same manner as in Example 1.

Example 13

In addition, an experiment was conducted under the same conditions as inExample 12 except that in place of silicon nanoparticles ground in twosteps, silicon nanoparticles ground in one step, i.e. the same siliconnanoparticles as those used in Example 1, were used as a solidpreparation.

Reference Example 2

As Reference Example 2, an experiment was conducted under the sameconditions as in Example 12 except that in place of siliconnanoparticles, silicon particles that were not finely divided, i.e.silicon particles having a diameter of 5 μm, were used.

FIG. 7 shows results in Examples 12 and 13, and Reference Example 2. Theresults in Examples 1 and 12 showed that even silicon nanoparticles thatare not subjected to a surface treatment generated hydrogen. Inaddition, when silicon nanoparticles ground in two stages were reactedfor 12 hours, the hydrogen generation amount was 262 ml per 1 mg ofsilicon nanoparticles, which was larger than the hydrogen generationamount (149 ml) with silicon nanoparticles ground in one step. On theother hand, for silicon particles which were not finely divided, and didnot have a particle diameter in a nanometer order, the hydrogengeneration amount with a reaction time of 12 hours was only 4.8 ml.These experiments showed that the hydrogen generation amount increasedas the crystallite diameter of silicon nanoparticles decreased. It isworth noting that in any of the above-described examples, hydrogen iscontinuously generated for at least 12 hours.

As described above, a solid preparation containing silicon fineparticles at least partially assume a powdery form, and can generatehydrogen in a water-containing liquid having a pH value of 7 or more.The solid preparation is orally administered to enter gastrointestinaltracts including the stomach and the intestines in an animal, and isgradually disintegrated by passing the inside of the stomach under aso-called acidic condition with a pH value of less than 7. In thegradually disintegrated solid preparation (including disintegratedproducts thereof, generation of hydrogen is promoted to generate a largeamount of hydrogen in the small intestine and subsequent tracts wherepancreatic fluid is secreted, and the pH value is in an alkali range ofmore than 7 (particularly, an alkali range of more than 7.4). The upperlimit of the pH value is not particularly limited, but for example,considering that the pH value as a bath salt is preferably in a range of11 or less, and the pH value as potable water is preferably in a rangeof 9 or less, the pH value is preferably less than 11.

Therefore, for example, the solid preparation in each of the embodimentsor each of the examples suppresses generation of a hydrogen gas in thestomach, and generates a large amount of hydrogen after passing throughthe stomach. Thus, according to each of the embodiment or each of theexamples, hydrogen necessary for reducing active oxygen or eliminatingactive oxygen in the body while suppressing generation of a hydrogen gasin the stomach is supplied in the small intestine and subsequent tracts.As a result, the solid preparation in each of the embodiments or each ofthe examples can greatly contribute to reduction of active oxygen orelimination of active oxygen.

One aspect of the method for producing a solid preparation includes thestep of finely dividing silicon particles having a crystal graindiameter of more than 1 μm by a physical grinding method, so that thesilicon particles are formed into silicon fine particles having acrystallite diameter principally of 1 nm or more and 100 nm or less. Thesolid preparation obtained by the production method mainly includessilicon fine particles, and exhibits a capability of generating hydrogenin an amount of 3 mug or more when the silicon fine particles arebrought into contact with a water-containing liquid having a pH value of7 or more. In one preferred aspect of the production method, the siliconfine particles form a main component of the solid preparation. Inaddition, a preferred example of a physical grinding method is a methodfor grinding particles by a bead mill grinding method, a planetary ballmill grinding method, a jet mill grinding method, or a combination oftwo or more thereof. However, from the viewpoint of production cost orease of production control, a-particularly preferred example is only abead mill grinding method or a grinding method including at least a beadmill grinding method.

In each of the embodiments and examples, a tablet is employed as oneexample of the solid preparation, but the target in each of theembodiments and examples is not limited to the tablet. Even when other“lump preparation” (e.g. capsule preparation), or solid preparationssuch as granular and powdered preparations which assume a powdery formrather than a lump form, i.e. one other example of a solid preparation,is employed, at least a part of the effect of each of the embodimentsand examples can be exhibited.

In each of the embodiments, isopropyl alcohol (IPA) is used for finelydividing the Si powder in the bead mill apparatus, but the type ofliquid for dispersing the Si powder in finely dividing the Si powder isnot limited to isopropyl alcohol (IPA). For example, even when ethanol(e.g. 99.5 wt %) is employed in place of isopropyl alcohol (IPA), thesame effect as the effect based on the first embodiment can beexhibited. In addition, in the fourth embodiment, a hydrofluoric acidaqueous solution is used, but the liquid in which silicon nanoparticlesare immersed in the fourth embodiment is not limited to a hydrofluoricacid aqueous solution. For example, by immersing silicon nanoparticlesfor about 30 minutes in a hydrogen peroxide solution (e.g. 100 mL of 3.5wt % hydrogen peroxide water contained in a Pyrex (registered trademark)glass container and heated to about 75° C.) in place of a hydrofluoricacid aqueous solution, the same effect as the effect based on the fourthembodiment can be exhibited. As described above, use of ethanol and/orhydrogen peroxide water is one preferred aspect in that hydrogen can begenerated by using a safer and more secure material (e.g. having lessinfluence on the human body).

INDUSTRIAL APPLICABILITY

The solid preparation of the present invention can also be used asrearing animal, food animals, animals for medical use, fish forculturing or the like. Further, the solid preparation can be used as anindustrial chemical or agent. The solid preparation can also be used asa human supplement or food additive.

The invention claimed is:
 1. A solid preparation comprising silicon fineparticles and the following (a) or (b): (a) an organic acid; (b) acovering layer which is not dissolved in a stomach and is dissolved in asmall intestine and/or a large intestine, and the solid preparation hasa capability of generating hydrogen.
 2. A solid preparation whichcomprises silicon fine particles having a crystallite diameter of 1 nmor more and 100 nm or less, and exhibits a capability of generatinghydrogen in an amount of 3 ml/g or more when brought into contact with awater-containing liquid having a pH value of 7 or more.
 3. The solidpreparation according to claim 2, further comprising a pH valueadjusting agent which causes the water-containing liquid to have a pHvalue of more than 7.4.
 4. The solid preparation according to claim 3,wherein the pH value adjusting agent is sodium hydrogencarbonate.
 5. Thesolid preparation according to claim 1, which is a capsule preparationin which the silicon fine particles are encapsulated, or a tablet formedso that the silicon fine particles are in a lump form.
 6. A method forproducing a solid preparation, the method comprising the step of finelydividing silicon particles having a crystal grain diameter of more than1 μm by a physical grinding method, so that the silicon particles areformed into silicon fine particles, the solid preparation comprisingsilicon fine particles and the following (a) or (b): (a) an organicacid; (b) a covering layer which is not dissolved in a stomach and isdissolved in a small intestine and/or a large intestine, and the solidpreparation has a capability of generating hydrogen.
 7. The method forproducing a solid preparation according to claim 6, wherein the physicalgrinding method is selected from a bead mill grinding method, aplanetary ball mill grinding method, a jet mill grinding method, and acombination thereof.
 8. A method for generating hydrogen, the methodcomprising: a first contact step of bringing a solid preparation, havinga capability of generating hydrogen, which comprises silicon fineparticles and the following (a) or (b): (a) an organic acid; (b) acovering layer which is not dissolved in a stomach and is dissolved in asmall intestine and/or a large intestine, into contact with a firstwater-containing liquid having a pH of less than 7; and a second contactstep of bringing the fine silicon particles into contact with a secondwater-containing liquid having a pH value of 7 or more after the firstcontact step.
 9. The method for generating hydrogen according to claim8, wherein the solid preparation is brought into contact with the secondwater-containing liquid at 35° C. or higher and 45° C. or lower.
 10. Themethod for generating hydrogen according to claim 8, wherein the solidpreparation is brought into contact with the second water-containingliquid having a pH value of 8 or more.
 11. The method for generatinghydrogen according to claim 8, wherein the solid preparation is oneselected from the group consisting of a capsule preparation in which thesilicon fine particles are encapsulated, and a tablet formed so that thesilicon fine particles are in a lump form.
 12. The method for generatinghydrogen according to claim 8, the method further comprising the step ofcausing a rearing animal to ingest the solid preparation, the solidpreparation being disintegrated in gastrointestinal tracts of therearing animal.